With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug–drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITD^mut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease.

随着血液学和肿瘤学中新型靶向药物的出现，患者的预后得到改善。由于易于发生药物相互作用 (DDI) 的药理学特征，与抗真菌预防治疗相结合对临床医生提出了挑战。Midostaurin 是FLT3 -TKD/-ITD ^mut的新型药物- 急性髓系白血病 (AML) 并通过细胞色素 P450 3A4 (CYP3A4) 代谢。泊沙康唑是一种标准的护理抗真菌剂，用于 AML 诱导治疗期间的预防，也是一种强效 CYP3A4 抑制剂。两种药物的同时给药导致米司他林暴露升高。这两种药物都可以在需要治疗的人数较少的情况下提高总体生存率。CYP3A4 相关 DDI 的影响仍有待确定。已观察到严重的不良事件；但是，尚不清楚它们是否可以直接与 DDI 相关联。缺乏评估侵袭性真菌感染发生率和 DDI 临床影响的前瞻性临床研究导致忽视挽救生命的抗真菌预防。已经提出了将两种药物联合使用的管理策略，但关于使用哪种方法的证据很少。在这次审查中，我们讨论了在特定临床环境中同时使用米多林和泊沙康唑的几种方法，并给出了日常临床实践中的例子。在 DDI 的背景下，治疗药物监测对于个体化和个性化抗肿瘤伴随治疗和抗真菌治疗将变得越来越重要。在临床试验中解决这个问题的制药公司可能会在这一领域发挥先锋作用。其他最近开发和批准的用于治疗 AML 的药物可能具有 DDI 的潜力，这标志着未来治疗这种威胁生命的疾病的可预见问题。在 DDI 的背景下，治疗药物监测对于个体化和个性化抗肿瘤伴随治疗和抗真菌治疗将变得越来越重要。在临床试验中解决这个问题的制药公司可能会在这一领域发挥先锋作用。其他最近开发和批准的用于治疗 AML 的药物可能具有 DDI 的潜力，这标志着未来治疗这种威胁生命的疾病的可预见问题。在 DDI 的背景下，治疗药物监测对于个体化和个性化抗肿瘤伴随治疗和抗真菌治疗将变得越来越重要。在临床试验中解决这个问题的制药公司可能会在这一领域发挥先锋作用。其他最近开发和批准的用于治疗 AML 的药物可能具有 DDI 的潜力，这标志着未来治疗这种威胁生命的疾病的可预见问题。